The central nervous system consists of a vast array of cells and synapses which depend on a delicate and precise chemical balance for normal function. Disruption of this chemical balance underlies diseases of the nervous system including the major neuropsychiatric disorders. However, because of the complexity of the central nervous system it remains difficult to define precisely the molecular content of nerve cells and synapses in normal or disease states. The long-term objective of this research program is to develop and implement new instrumentation with greatly increased capability for micro-separation and ultra-sensitive of the chemical content of neurons. Capillary electrophoresis, either free zone or gel-packed, will be used to fractionate molecules from single neurons, synapses, neuronal releasates, or individual synaptic vesicles. Analytes will be quantitated by optical means using laser induced fluorescence and laser opto-thermal deflection in conjunction with charge coupled detector devices. It may be possible to perform analyses which are greater than one million fold more sensitive than current techniques.